Prognostic Relevance of Concordant Expression CD69 and CD56 in Response to Bortezomib Combination Therapy in Multiple Myeloma Patients

Cancer Invest. 2021 Oct;39(9):777-782. doi: 10.1080/07357907.2021.1964521. Epub 2021 Aug 25.

Abstract

Objective: Multiple myeloma is an incurable hematological malignancy. Currently, the use of proteasome inhibitors could be superior to chemotherapy-based regimen in the treatment of this disease. However, resistance to bortezomib combination therapy still occurs in some patients. So, this research work aims to assess CD69 and CD56 expression in these cases and their relation to the response to therapy.

Materials and methods: Immunophenotyping by 4-color multi-parameter flow cytometry was carried out on 98 multiple myeloma cases. Clonal plasma cells were gated by co-expression of CD38 with CD138 with low SSC, negative or dim CD45.

Results: Double negative CD69 and CD56 (47.9%) multiple myeloma cases were associated with high serum β2 microglobulin, creatinine, calcium and low serum albumin. There was also a significant correlation between the absence of these markers with osteolytic lesions and unfavorable cytogenetic t (4;14) (p < 0.001). Moreover, there was a highly significant correlation between CD69- and CD56- with non-response to bortezomib combination therapy in multiple myeloma patients (p < 0.0001). Regression analysis for the prediction of non- response to treatment in these cases using different prognostic indicators revealed that high serum β2 microglobulin, unfavorable cytogenetic, advanced stage, and low expression of CD69 and CD56 were poor predictors of non-response.

Conclusion: CD69 in association with CD56 could be an independent prognostic factor in multiple myeloma cases. It could be used in the routine laboratory assessment for refining stratification and timely therapeutic decision for highly cost therapy in developing countries.

Keywords: Bortezomib; CD56; CD69; proteasome inhibitors; resistance.

MeSH terms

  • Aged
  • Antigens, CD / metabolism*
  • Antigens, Differentiation, T-Lymphocyte / metabolism*
  • Antineoplastic Agents / therapeutic use*
  • Bortezomib / administration & dosage
  • CD56 Antigen / metabolism*
  • Female
  • Flow Cytometry / methods
  • Humans
  • Immunophenotyping / methods
  • Kaplan-Meier Estimate
  • Lectins, C-Type / metabolism*
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / metabolism
  • Prognosis

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Antineoplastic Agents
  • CD56 Antigen
  • CD69 antigen
  • Lectins, C-Type
  • Bortezomib